It is estimated that between 100,000 and 200,000 people with epilepsy in the United States are potential candidates for surgical treatment; however, less than 3,000 receive surgery each year. Neuroimaging and EEG telemetry advances have greatly enhanced safety and efficacy of surgical intervention for epilepsy, and reasons for the continued apparent underutilization of this treatment modality are unclear. This must be attributable in part to the fact that surgical treatment is generally considered to be a "last resort" approach for patients with medically intractable seizures. Because there are so many antiepileptic drugs now available, it would take several lifetimes to carry out appropriate trials of each, as monotherapy and in combination, on any given patient Consequently, a randomized clinical trial (RCT) designed to determine when to offer surgical treatment for epilepsy would have a major positive influence on appropriate and timely referral. A RCT for epilepsy surgery has never been performed for any reason, primarily because epilepsy surgery teams have considered it unethical to deny surgery to those with medically refractory seizures who have been fully evaluated and found to be surgical candidates. Several recent developments make it now possible to design an ethically justifiable RCT: 1) A number of surgically remediable epileptic syndromes have been defined which have a poor response to antiepileptic drug treatment, but have a 70 to 90 percent chance of remission with surgical intervention; 2) Mesial temporal lobe epilepsy (MILE), the prototypic surgically remediable syndrome, is by far the most common form of epilepsy treated surgically in the U.S.; 3) Anecdotal data over many decades, and preliminary data from a few recent studies, suggest that early surgical intervention provides the best opportunity to completely eliminate habitual seizures and prevent or reverse disabling psychosocial consequences; 4) True equipoise exists, however, concerning the benefits of early surgical treatment over further medical treatment (within the first two years of refractoriness to first-line medications). This application requests funds to plan a multicenter RCT to test the hypothesis that: Patients who receive surgical intervention for MTLE within two years of failing first- line drugs will have better quality of life and will be more likely to become seizure free after two years, compared with those continuing on medical treatment. Twelve epilepsy surgery centers with ties to UCLA, the Clinical Trials Coordinating Center of the University of Rochester, and a multidisciplinary steering committee have already begun the planning process outlined.